Simvastatin does not alleviate muscle pathology in a mouse model of Duchenne muscular dystrophy
| Autor: | Paulina Podkalicka, Katarzyna Kaziród, Jozef Dulak, Agnieszka Łoboda, Emilia Samborowska, Olga Mucha |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
musculoskeletal diseases
Duchenne muscular dystrophy mdx mouse medicine.medical_specialty congenital hereditary and neonatal diseases and abnormalities Simvastatin 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors Diseases of the musculoskeletal system Dystrophin Mice angiogenesis Gastrocnemius muscle Internal medicine DMD medicine Animals simvastatin Orthopedics and Sports Medicine Muscle Skeletal Myopathy Molecular Biology 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors biology business.industry Research Muscle weakness Cell Biology medicine.disease Muscular Dystrophy Duchenne Disease Models Animal Endocrinology RC925-935 Mice Inbred mdx biology.protein Creatine kinase Angiogenesis medicine.symptom business mdx medicine.drug |
| Zdroj: | Skeletal Muscle, Vol 11, Iss 1, Pp 1-16 (2021) Skeletal Muscle |
| ISSN: | 2044-5040 |
| Popis: | Background Duchenne muscular dystrophy (DMD) is an incurable disease, caused by the mutations in the DMD gene, encoding dystrophin, an actin-binding cytoskeletal protein. Lack of functional dystrophin results in muscle weakness, degeneration, and as an outcome cardiac and respiratory failure. As there is still no cure for affected individuals, the pharmacological compounds with the potential to treat or at least attenuate the symptoms of the disease are under constant evaluation. The pleiotropic agents, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, known as statins, have been suggested to exert beneficial effects in the mouse model of DMD. On the other hand, they were also reported to induce skeletal-muscle myopathy. Therefore, we decided to verify the hypothesis that simvastatin may be considered a potential therapeutic agent in DMD. Methods Several methods including functional assessment of muscle function via grip strength measurement, treadmill test, and single-muscle force estimation, enzymatic assays, histological analysis of muscle damage, gene expression evaluation, and immunofluorescence staining were conducted to study simvastatin-related alterations in the mdx mouse model of DMD. Results In our study, simvastatin treatment of mdx mice did not result in improved running performance, grip strength, or specific force of the single muscle. Creatine kinase and lactate dehydrogenase activity, markers of muscle injury, were also unaffected by simvastatin delivery in mdx mice. Furthermore, no significant changes in inflammation, fibrosis, and angiogenesis were noted. Despite the decreased percentage of centrally nucleated myofibers in gastrocnemius muscle after simvastatin delivery, no changes were noticed in other regeneration-related parameters. Of note, even an increased rate of necrosis was found in simvastatin-treated mdx mice. Conclusion In conclusion, our study revealed that simvastatin does not ameliorate DMD pathology. |
| Databáze: | OpenAIRE |
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